Interleukin 1 suppresses inflammation in rabbit colitis. Mediation by endogenous prostaglandins.
Pretreatment with low-dose IL-1 has protective effects in animal models of inflammation or tissue injury, but the mechanisms of these protective effects are not established. To determine if prostaglandins are involved, we administered human recombinant IL-1 beta and measured rectal PGE2 production in rabbits with formalin-immune complex colitis. IL-1 beta (0.3 micrograms/kg) administered 24 h before induction of colitis increased PGE2 (231 +/- 36 to 1,299 +/- 572 pg/ml, P less than 0.01) and reduced subsequent inflammatory cell infiltration index (from 2.8 +/- 0.3 to 1.4 +/- 0.3, P less than 0.02) and edema (from 2.5 +/- 0.3 to 1.3 +/- 0.3, P less than 0.01) compared with vehicle-matched animals. Administration of ibuprofen (10 mg/kg i.v.) together with IL-1 beta prevented the stimulation of PGE2 and the reduction in inflammation. Colonic PGE2 production correlated inversely with subsequent severity of inflammation (P less than 0.02, r = -0.39) and edema (P less than 0.04, r = -0.35). IL-1-administration 30 min before induction of colitis did not affect the severity of inflammation. Similarly, pretreatment with a noninflammatory synthetic peptide (fragment 163-171) of human IL-1 beta, either 30 min or 24 h before colitis induction, did not reduce inflammation or increase prostaglandin synthesis. These data demonstrate that pretreatment with IL-1 beta 24 h before the induction of colitis reduces inflammation by a mechanism that requires prostaglandin synthesis.
Cominelli
F
F
Department of Medicine, Harbor University of California Los Angeles Medical Center, Torrance 90502.
Nast
C C
CC
Llerena
R
R
Dinarello
C A
CA
Zipser
R D
RD
D000818:Animals; D003092:Colitis / Q000378:metabolism / Q000628:therapy*; D015232:Dinoprostone / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D053583:Interleukin-1beta; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology
D007375:Interleukin-1; D053583:Interleukin-1beta; D010446:Peptide Fragments; D011994:Recombinant Proteins; C052994:interleukin-1beta (163-171); D015232:Dinoprostone; D007052:Ibuprofen